Researchers at the HudsonAlpha Institute for Biotechnology, along with an international team of collaborators from six countries, have identified a new genetic disorder that causes intellectual and developmental delay in children. GeneMatcher, an online "matchmaking" system for scientists researching rare genetic variants, connected the team members. The research is published online in the American Journal of Human Genetics.

"Essentially, we did experiments to understand how variants in the EBF3 gene might change its function during development," said Drew Hardigan, a graduate student in the Myers Lab at HudsonAlpha and a co-lead author. "The role of EBF3 had been studied in terms of neural development, but had not been previously described as a gene in which mutations cause intellectual delay. We were able to demonstrate that changes to the gene are the cause of a clinical disorder."

EBF3 was identified at HudsonAlpha as an interesting gene for research through a pediatric genomics program led by Greg Cooper, PhD. Through genomic sequencing, Cooper's lab had identified two patients with changes to EBF3. However, his team could not find any similar cases or publications on the gene to confirm the variants were causing the patients' symptoms. The genetic changes were labeled variants of uncertain significance, or a VUSs.

The group turned to the website GeneMatcher, which operates like a matchmaker site for scientists interested in genetic variants. Using the online system, Cooper's team was able to contact researchers around the world who were also interested in VUSs in EBF3. Once connected, the international group performed a statistical analysis confirming the gene was likely the cause of the symptoms for 10 patients located on three continents. The group then used a variety of genomic assays to investigate the function of the variants.

The experiments demonstrated that the genetic changes to EBF3 - the same changes found in those 10 patients - disrupt important functions required for normal development. They also found that changes in this gene were likely the cause of about one in every 1,000 patients with unexplained neurodevelopmental disorders.